1. Field of the Invention
The present invention relates to novel sulfonated sugar compounds and pharmaceutical compositions containing the same. The present invention also relates to novel methods of making such a compound and novel intermediates useful for making such a compound. The present invention further relates to novel methods for treating a tumor by administering such a compound.
2. Discussion of the Background
At present, in Japan, malignant tumors, cardiac disease, and cerebrovascular disease are responsible for about 60 percent of deaths. Among them, malignant tumor is the leading cause of death and is increasing. For treating malignant tumors, the three major therapies are surgical therapy, chemotherapy, and radiation therapy. In recent years, the quality of life (QOL) of a patient has been emphasized, and much attention is being paid to radiation therapy.
In common radiation therapy, halogenated pyrimidine and hypoxic cell sensitizers are known as chemical or pharmaceutical substances administered simultaneously with radiation thereby enhancing its therapeutic effect, more specifically, as clinically applicable radiosensitizers (for example, see Radiobiology for the Radiologist (Fourth Edition), Eric J. Hall et al, J. B. Lippincott Company (“Houshasennkainotameno Hoshasenseibutsugaku”, translated by Muneyasu Urano, Shinoharashinsha. Inc.). Examples of known halogenated pyrimidines include 5-iododeoxyuridine. Examples of known hypoxic cell sensitizers include misonidazole. However, these known radiosensitizers are scarcely in actual use, because they produce side effects such as gastrointestinal disorders and peripheral neurotoxicity, and involve other outstanding problems.
On the other hand, novel radiosensitizers composed of sulfopyranosylacylglycerol or salts thereof are disclosed in Jpn. Pat. Appln. No. 2004-374445. However, in sulfopyranosylacylglycerols, the 2-position carbon atom in the glycerol moiety is an asymmetric carbon, so that the stereostructure cannot be controlled by a relatively inexpensive and simple synthesis process as described in Jpn. Pat. Appln. No. 2004-374445, in which the terminal double bond of an allyl group is dihydroxylated to form a glycerol skeleton. Therefore, R/S diastereomers are generated at a ratio of about 1:1. In order to solve the problem, respective diastereomers can be independently synthesized, but such process requires bonding of a glycerol derivative having a definite stereostructure to a sugar derivative during synthesis, which results in the complication of the synthesis process and an enormous increase of the cost.
In addition, a sulfopyranosylacylglycerol derivative generates an R/S diastereoisomer (diastereomers) at the 2-position of the glycerol moiety, as well as several percent of a structural isomer (2-acyl isomer) wherein the acyl group at the 1-position of glycerol has been transferred to the 2-position between and/or within the molecules. These 2-acyl isomers are generated during synthesis and storage in a solution. Therefore, even if the respective diastereomers are independently prepared, it is very difficult to provide a high purity sulfopyranosylacylglycerol derivative.
Although a sulfopyranosylacylglycerol derivative exhibits a noticeable radiosensitization effect, its development as a drug will entail very difficult situations due to problems with synthesis and physical properties.